Preparation of solutions of medicaments insoluble or sparingly soluble in water



Patented Dec. 22, 1942 UNITED STATES PATENT OFFlCE PREPARATION OF SOLUTIONS OF MEDICA- MIENTS INSOLUBLE R SPARINGLY SOLU BLE IN WATER Werner Ursum; Frankiort-on-the-Main,

Ger-

, many; vested in the Alien Property Custodian N 0 Drawing.

Application January 9, 1939, Serial No. 250,065. In Germany November 12, 1935 6 Claims. (01. 167-52) The extraordinarily surprising observation, which was not at all expected, has been made that a mixture of medicinal substances has va quite substantially greater solubility in aqueous needs for practical purposes solutions of much higher concentration.

It is possible according to the present method, to obtain solutions of 20% and more, so that for purposes of injection, a sufllcient quantity of eiiective substances can be dissolved in a small volume. According to the present method, there is obtained not only the use in high concentrations, but also the increase in eflect by a suitable combination.

The common medicinal substances used for the manufacture of the concentrated solutions. may either work in the same direction and belong for example to the same class of substances, or have therapeutically different points of attack. Thus, undesired subsidiary efiects by substances only increasing the solubility, are thus excluded.

The solutions thus obtained enable the easy application of a strongly acting dose, suillcient for each case. A special advantage of the present process is the fact that undesirable solvents not sufllc'iently definite or not definite in their effects may be avoided. There results, therefore, in the use of the solutions made in accordance with the invention no unknown reactions of any kind in the medical or clinical practice, since for the dissolution of the hypnotic solution only urethane (ester of carbonic acid) to ether with water is used.

The following examples show my invention without limiting it thereto:

Water If both mixtures are mixed together, there is quickly produced a clear and durable solution, which is also not influenced by heating.

The solution contains over 20% by weight of strong hypnotics, can be injected without irritation and results in a strong and lasting sleep.

- 1 Example 2 A mixture of Parts by weight Diethylbarbituric acid l5 Diethyltetrabromoethaneurea 7 Ethylur 60 Water 18 effect of this solution is emphasized.

Example 3 I A 30% solution of various barbituric acid derivatives is obtained by mixing of:

- Parts by weight Diethylbarbituric acid 10 Diallylbarbituric acid l0 Phenylethylbarbituric acid 10 Ethylurefhane 54 Water 16 Rapid liquefying and solving takes place; the solution obtained may be sterilized and injected.

Example 4 Parts by weight Diethylbarbituric acid 15 chloral hydrate 15 Ethyluretha Water 10 give a clear and durable solution.

Example 5 Parts by weight Z-Phenylquinoline-4-methylcarboxylic acid- 10 Urethane 55 Water 15 do not dissolve. With an addition of 20 parts by weight oi camphor, there is produced a clear and durable solution.

I claim:

1. Method for the manufacture of durable concentrated solutions of organic medicinal substances not easily soluble in water using ethylurethane as a solvent, wherein at least two of the group containing diethylbarbituric acid, diallylbarbituric acid, diethyltetrabromoethanourea, and phenylethylbarbituric acid are dissolved in quantities of ethylurethane and water insumcient to form a solvent for a single one of said substances.

2. That method of preparing a medicinal solution which consists in mixing by weight Parts by weight Diethylbarbituric acid 6 Ethylurethane 18 Water 6 then mixing by weight Parts by weight A Diallylbarbituric acid 3 Ethylurethane 9 Water 3 and then mixing the two mixtures.

3. That method of preparing a medicinal solu-- tion which consists in mixing by weight Parts by weight Diethylbarbituric acid 15 Diethyltetrabromoethanourea '7 Ethvlurethane 60 Water 18 4. That method of preparing a medicinal solution which consists in mixing by weight 5. A solution of a mixture of several barbituric acid derivatives with a combination of urethanes and water in such proportions that the quantity of the urethane and water is insuilicient to effect complete solution of any one of the barbituric acid derivatives composing the mixture, whereby the solution thus obtained is permanently stable, sterilizable and usable for medical purposes.

6. A solution of a mixture of diethylbarbituric acid and diallylbarbituric acid with a combination of ethylurethane and water in such proportions that the quantity of ethylurethane and water is insuiflcient to efiect complete solution of the diethylbarbituric acid or the diallylbarbituric acid when unmixed, whereby the resulting solution is permanently stable, sterilizable and usable for medical purposes.

WERNER URSUM. 

